Renal and ureteral stone disease comprises a fairly common disorder of the urinary tract with detrimental consequences to the afflicted patient ranging in degrees of severity. Often referred to as varying forms of nephrolithiasis, this disorder is often characterized, in part, based on the composition of the stone formed in the kidney or ureter. If left untreated, a renal stone can cause damage to the kidneys and potentially lead to kidney failure, among other maladies.
Although the etiology of nephrolithiasis remains elusive, several aspects of the process of stone formation are known. Supersaturated urine is generally required for stone formation, which itself is known to depend on urinary pH, ionic strength, solute concentration and complexation, among other factors. See M. J. Stoller, Urinary Stone Disease, in SMITH'S GENERAL UROLOGY 256-262 (E. A. Tanagho & J. W. McAninch eds., 16th ed. 2004). Moreover, a variety of ions and solutes can contribute to stone formation (e.g., calcium, oxalate, phosphate, uric acid, sodium, etc.), with calcium being the major ion present in urinary crystals. Generally, 80%-85% of all renal stone patients have calcareous renal stones. See id. at 257, 259. Although a variety of factors affect the probability of renal stone formation, having an increased concentration of calcium ions in urine (e.g., hypercalciuria) will likewise increase the probability of the formation of stones.
In general, almost all (i.e., between about 95%-99%) of the calcium filtered at the glomerulous is reabsorbed between the proximal tubules, the loop of Henle and the distal and collecting tubules. The distal tubule cells are known to be responsible for the retention and excretion of calcium (to maintain calcium hemostasis). In normal conditions, calcium that is not reabsorbed into the blood stream is excreted in the urine. When lower concentrations of filtered calcium are reabsorbed, there is an increase in the calcium ion concentration in the urine, thus increasing the likelihood of the formation of renal stones.
It has interestingly been recognized that subjects who develop renal stones at one point, and are optionally treated for them, are at an increased risk of developing stones again. Recurrence rates in these subjects are as high as 50-60%, or more.
Early detection of an increased risk of stone formation would permit the institution of preventative and conciliatory measures such as increased water consumption, diet modification (e.g., avoiding foods rich in calcium and/or avoiding the consumption of foods high in oxalates such as cola, coffee, chocolate, nuts, spinach, strawberries, wheat bran, tea, etc.) or beginning medical treatment. Moreover, as the reoccurrence of renal stones in individual patents is high, it is important to have advance indicators for the progress of treatment modalities to ensure appropriate tailoring and success.
Accordingly, there exists a need in the art for early and accurate identification of the risk of developing renal stones in a subject. The present invention addresses this and other related needs in the art.